The cDNA's for several steroid hormone receptors have been cloned and expressed in heterologous cells. The subsequent development of cell transfection assays to analyze receptor mutants has enabled the definition of the functional domains of the receptors. It is clear that they contain distinct domains for DNA and hormone binding. We wish to further define the critical amino acids within these structures required for ligand and DNA binding. This will be accomplished using two complementing strategies. The first is a physical-biochemical (X-ray diffraction and 2D NMR) analysis of the receptor. This requires large quantities of purified protein. For this we propose to use Saccharomyces cerevisiae to overproduce the receptor. The second is to identify mutants of the receptor by designing genetic strategies that will identify key structural components within the molecule. Traditionally endocrinologists have used animal and avian models to study steroid hormone action and as sources of receptor for structural and biochemical analysis. The demand for pure receptor is increasing. Recently however, we have accumulated data to suggest that it may be possible to develop Saccharomyces cerevisiae as a high connectivity model for steroid hormone action. Furthermore, advances in this area we believe, will encourage further use of yeast in related areas, with a commensurate decrease in the use of animal models.